Heart Failure: Epidemiology, Pathophysiology, and Management

Figures

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  FIGURE 1. Mechanisms of calcium regulating proteins in physiological and pathological states (heart failure). All Ca2+ amounts in normal and HF were unified, where Ca2+ concentration in normal cardiomyocyte was as follows: SR > extracellular > cytoplasm, and Cart concentration in HF was as follows: cytoplasm > extracellular > SR. The flow of Ca2+ during systole/diastole is plotted, and the rising and falling trend of cytosolic Ca2+ during systole/diastole is indicated by arrows. Orange arrowheads indicate the direction of ion flux during systole, whereas green arrowheads denote the direction during diastole.

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  FIGURE 2. Pathological differences in calcium regulating proteins between HFrEF and HFpEF. At the molecular level, the forward and reverse modes of NCX are illustrated, together with the differential expression and posttranslational modifications of SERCA2a, RyR2, PMCA, and LTCC, as well as the distribution pattern of LTCC. At the functional level, CaT dynamics and sarcomeric states during systole and diastole are depicted. Orange arrowheads indicate the direction of ion flux during systole, whereas green arrowheads denote the direction during diastole.

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  FIGURE 3. Mechanisms of calcium homeostasis‐related signaling pathways in physiological and pathological states (heart failure). The diagram illustrates the interactions of the cAMP, cGMP, CaMKII, RAS, and PI3K pathways with calcium regulating proteins and calcium ions. Blue highlights denote cGMP microdomains (GC‐A and GC‐B), whereas red highlights denote cAMP microdomains. Under physiological conditions, cGMP microdomains predominate over cAMP microdomains; in HF, this relationship is reversed. The balance between the two influences calcium regulating proteins. In addition, the figure depicts how the CaMKII, RAS, and PI3K pathways differentially contribute to physiological versus pathological cardiac hypertrophy.

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  FIGURE 4. Pathological differences in calcium homeostasis‐related signaling pathways between HFrEF and HFpEF. The diagram depicts the differences in the cGMP pathway (GC‐A and GC‐B) between HFrEF and HFpEF, as well as the distinct interactions of the cAMP, CaMKII, Ras, and PI3K pathways with calcium regulating proteins.

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  FIGURE 5. Pathophysiological mechanism network in heart failure. Starting from calcium homeostasis, calcium‐regulating proteins, or calcium‐related pathways interact with other mechanisms to jointly drive the onset and progression of heart failure.